OBJECTIVE: To develop methods for the chemical synthesis of stereochemically complex medium- and large-ring carbocyclic compounds, and the application of these methods to the total synthesis of anti-neoplastic and biologically important macrocyclic natural products. APPROACH AND PROGRESS: Several methods for the stereoselective elaboration of acyclic carbon chains are being studied, and applied toward the synthesis of the anti-tumor rifamicins, the anti-leukemic Maytenus macrolides, nonactic acid, and the aglycone of the erythromycin antibiotics. These methods include a sequence for the stereospecific homologation of substituted homoallylic alcohols, stereocontrolled additions to Beta-hydroxycarbonyl chelates and conjugate displacement reactions of substituted cyclopropyloxiranes. Additionally, a recently developed method for the synthesis of Gamma-oxo-Alpha,Beta-unsaturated lactones is being used in the synthesis of Brefeldin A. BIBLIOGRAPHIC REFERENCES: Paul A. Bartlett, "Synthesis of beta-Acylacrylic Esters and alpha,beta-Butenolides via beta-Ketosulfoxide Alkylation", J. Amer. Chem. Soc., 98, 3305 (1976).